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用于增强协同牙周声动力化疗的载米诺环素二氧化钛纳米颗粒

Minocycline-Loaded Titanium Dioxide Nanoparticles for Augmented Synergistic Periodontal Sonodynamic Chemotherapy.

作者信息

Huang Shuying, Xia Chengyao, Zuo Wenbao, Wang Rui, Xu Nuo, Ye Wenxin, Li Xiao, Chen Yong, Zhu Xuan

机构信息

Xiamen University School of Public Health, Xiamen, People's Republic of China.

Department of Stomatology, School of Medicine, Xiamen University, Xiamen, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Mar 5;20:2727-2741. doi: 10.2147/IJN.S501964. eCollection 2025.

Abstract

BACKGROUND

The current clinical treatment of periodontitis usually involves mechanical removal of pathogenic bacteria through ultrasonic scaling and root planing, supplemented with antibacterial medications to inhibit microbial overgrowth. However, the therapeutic efficiency remains unsatisfactory due to complicated periodontal anatomy, limited plaque removal, short retention of antibiotics, and related side effects.

METHODS AND RESULTS

To address these issues, we successfully synthesized mesoporous titanium dioxide nanoparticles (MTN) via a sol-gel method, which were modified with hemoglobin (Hb) and loaded with minocycline (MINO). The resulting Hb-MTN/MINO nanoparticles had a size of 215 nm, zeta potential of -19.8 mV±0.9 mV, and uniform shape with a PDI index of 0.176. The modification with hemoglobin (Hb) provided sufficient oxygen for antimicrobial sonodynamic therapy (aSDT), contributing to improved generation of reactive oxygen species (ROS) under low ultrasound intensity. After MINO loading, the system exhibited notable antibacterial efficacy, with a 6 log reduction of bacterial counts compared to the control group. Hb-MTN/MINO was evaluated in vivo in terms of oral index, soft and hard tissues, along with biosafety evaluation in periodontal disease model rats. Hb-MTN/MINO demonstrated a satisfactory therapeutic effect, whereby the periodontal condition of the rats exhibited a greater improvement than the control group, and measurement of the serum levels of inflammatory factors revealed that both IL-6 and MMP-9 were significantly downregulated.

CONCLUSION

These findings confirm the potential of Hb-MTN/MINO nanoparticles as a promising treatment option for periodontitis.

摘要

背景

目前牙周炎的临床治疗通常包括通过超声洁治和根面平整机械清除病原菌,并辅以抗菌药物以抑制微生物过度生长。然而,由于牙周解剖结构复杂、菌斑清除有限、抗生素滞留时间短以及相关副作用,治疗效果仍不尽人意。

方法与结果

为解决这些问题,我们通过溶胶 - 凝胶法成功合成了介孔二氧化钛纳米颗粒(MTN),并用血红蛋白(Hb)对其进行修饰,再负载米诺环素(MINO)。所得的Hb - MTN/MINO纳米颗粒尺寸为215 nm,zeta电位为 - 19.8 mV±0.9 mV,形状均匀,PDI指数为0.176。血红蛋白(Hb)修饰为抗菌声动力疗法(aSDT)提供了充足的氧气,有助于在低超声强度下提高活性氧(ROS)的生成。负载MINO后,该系统表现出显著的抗菌效果,与对照组相比细菌计数降低了6个对数级。在牙周病模型大鼠中对Hb - MTN/MINO进行了体内口腔指数、软组织和硬组织方面的评估以及生物安全性评估。Hb - MTN/MINO表现出令人满意的治疗效果,大鼠的牙周状况比对照组有更大改善,炎症因子血清水平测定显示IL - 6和MMP - 9均显著下调。

结论

这些发现证实了Hb - MTN/MINO纳米颗粒作为牙周炎一种有前景的治疗选择的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d1/11892737/6a3cb96d4991/IJN-20-2727-g0001.jpg

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